PYRG_BACTN
ID PYRG_BACTN Reviewed; 537 AA.
AC Q8AA75;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=CTP synthase {ECO:0000255|HAMAP-Rule:MF_01227};
DE EC=6.3.4.2 {ECO:0000255|HAMAP-Rule:MF_01227};
DE AltName: Full=Cytidine 5'-triphosphate synthase {ECO:0000255|HAMAP-Rule:MF_01227};
DE AltName: Full=Cytidine triphosphate synthetase {ECO:0000255|HAMAP-Rule:MF_01227};
DE Short=CTP synthetase {ECO:0000255|HAMAP-Rule:MF_01227};
DE Short=CTPS {ECO:0000255|HAMAP-Rule:MF_01227};
DE AltName: Full=UTP--ammonia ligase {ECO:0000255|HAMAP-Rule:MF_01227};
GN Name=pyrG {ECO:0000255|HAMAP-Rule:MF_01227}; OrderedLocusNames=BT_0590;
OS Bacteroides thetaiotaomicron (strain ATCC 29148 / DSM 2079 / JCM 5827 /
OS CCUG 10774 / NCTC 10582 / VPI-5482 / E50).
OC Bacteria; Bacteroidetes; Bacteroidia; Bacteroidales; Bacteroidaceae;
OC Bacteroides.
OX NCBI_TaxID=226186;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29148 / DSM 2079 / JCM 5827 / CCUG 10774 / NCTC 10582 /
RC VPI-5482 / E50;
RX PubMed=12663928; DOI=10.1126/science.1080029;
RA Xu J., Bjursell M.K., Himrod J., Deng S., Carmichael L.K., Chiang H.C.,
RA Hooper L.V., Gordon J.I.;
RT "A genomic view of the human-Bacteroides thetaiotaomicron symbiosis.";
RL Science 299:2074-2076(2003).
CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with
CC either L-glutamine or ammonia as the source of nitrogen. Regulates
CC intracellular CTP levels through interactions with the four
CC ribonucleotide triphosphates. {ECO:0000255|HAMAP-Rule:MF_01227}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-glutamine + UTP = ADP + CTP + 2 H(+) + L-
CC glutamate + phosphate; Xref=Rhea:RHEA:26426, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:37563, ChEBI:CHEBI:43474, ChEBI:CHEBI:46398,
CC ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.4.2;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamine = L-glutamate + NH4(+);
CC Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + NH4(+) + UTP = ADP + CTP + 2 H(+) + phosphate;
CC Xref=Rhea:RHEA:16597, ChEBI:CHEBI:15378, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:37563, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:46398, ChEBI:CHEBI:456216; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01227};
CC -!- ACTIVITY REGULATION: Allosterically activated by GTP, when glutamine is
CC the substrate; GTP has no effect on the reaction when ammonia is the
CC substrate. The allosteric effector GTP functions by stabilizing the
CC protein conformation that binds the tetrahedral intermediate(s) formed
CC during glutamine hydrolysis. Inhibited by the product CTP, via
CC allosteric rather than competitive inhibition. {ECO:0000255|HAMAP-
CC Rule:MF_01227}.
CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo pathway;
CC CTP from UDP: step 2/2. {ECO:0000255|HAMAP-Rule:MF_01227}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01227}.
CC -!- MISCELLANEOUS: CTPSs have evolved a hybrid strategy for distinguishing
CC between UTP and CTP. The overlapping regions of the product feedback
CC inhibitory and substrate sites recognize a common feature in both
CC compounds, the triphosphate moiety. To differentiate isosteric
CC substrate and product pyrimidine rings, an additional pocket far from
CC the expected kinase/ligase catalytic site, specifically recognizes the
CC cytosine and ribose portions of the product inhibitor.
CC {ECO:0000255|HAMAP-Rule:MF_01227}.
CC -!- SIMILARITY: Belongs to the CTP synthase family. {ECO:0000255|HAMAP-
CC Rule:MF_01227}.
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DR EMBL; AE015928; AAO75697.1; -; Genomic_DNA.
DR RefSeq; NP_809503.1; NC_004663.1.
DR RefSeq; WP_008763175.1; NZ_UYXG01000009.1.
DR AlphaFoldDB; Q8AA75; -.
DR SMR; Q8AA75; -.
DR STRING; 226186.BT_0590; -.
DR PaxDb; Q8AA75; -.
DR PRIDE; Q8AA75; -.
DR EnsemblBacteria; AAO75697; AAO75697; BT_0590.
DR GeneID; 60926547; -.
DR KEGG; bth:BT_0590; -.
DR PATRIC; fig|226186.12.peg.592; -.
DR eggNOG; COG0504; Bacteria.
DR HOGENOM; CLU_011675_5_0_10; -.
DR InParanoid; Q8AA75; -.
DR OMA; EFNNAYR; -.
DR UniPathway; UPA00159; UER00277.
DR Proteomes; UP000001414; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003883; F:CTP synthase activity; IBA:GO_Central.
DR GO; GO:0004359; F:glutaminase activity; IEA:RHEA.
DR GO; GO:0042802; F:identical protein binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006241; P:CTP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IBA:GO_Central.
DR CDD; cd03113; CTPS_N; 1.
DR CDD; cd01746; GATase1_CTP_Synthase; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.40.50.880; -; 1.
DR HAMAP; MF_01227; PyrG; 1.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR004468; CTP_synthase.
DR InterPro; IPR017456; CTP_synthase_N.
DR InterPro; IPR017926; GATASE.
DR InterPro; IPR033828; GATase1_CTP_Synthase.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11550; PTHR11550; 1.
DR Pfam; PF06418; CTP_synth_N; 1.
DR Pfam; PF00117; GATase; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00337; PyrG; 1.
DR PROSITE; PS51273; GATASE_TYPE_1; 1.
PE 3: Inferred from homology;
KW ATP-binding; Glutamine amidotransferase; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; Pyrimidine biosynthesis; Reference proteome.
FT CHAIN 1..537
FT /note="CTP synthase"
FT /id="PRO_0000266064"
FT DOMAIN 296..537
FT /note="Glutamine amidotransferase type-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT REGION 1..268
FT /note="Amidoligase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 384
FT /note="Nucleophile; for glutamine hydrolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 510
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT ACT_SITE 512
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 15
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 15
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 16..21
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 56
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 73
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 143
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 150..152
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 189..194
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 189..194
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 225
FT /ligand="CTP"
FT /ligand_id="ChEBI:CHEBI:37563"
FT /ligand_note="allosteric inhibitor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 225
FT /ligand="UTP"
FT /ligand_id="ChEBI:CHEBI:46398"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 357
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 385..388
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 408
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
FT BINDING 465
FT /ligand="L-glutamine"
FT /ligand_id="ChEBI:CHEBI:58359"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01227"
SQ SEQUENCE 537 AA; 59864 MW; 254563CCE4BE2A79 CRC64;
MGETKYIFVT GGVASSLGKG IISSSIGKLL QARGYNVTIQ KFDPYINIDP GTLNPYEHGE
CYVTVDGHEA DLDLGHYERF LGIQTTKANN ITTGRIYKSV IDKERRGDYL GKTIQVIPHI
TDEIKRNVKL LGNKYKFDFV ITEIGGTVGD IESLPYLESI RQLKWELGKN ALCVHLTYVP
YLAAAGELKT KPTQHSVKEL QSVGIQPDVL VLRAEHPLSD GLRKKVAQFC NVDDKAVVQS
IDAETIYEVP LLMQAQGLDS TILEKMGLPV GETPGLGPWR KFLERRHAAE TKEPINIALV
GKYDLQDAYK SIREALSQAG TYNDRKVEVH FVNSEKLTDE NVAEALKGMA GVMIGPGFGQ
RGIDGKFVAI KYTRTHDIPT FGICLGMQCI AIEFARNVLG YADADSREMD EKTPHNVIDI
MEEQKAITNM GGTMRLGAYE CVLQKGSKAY LAYGEEHIQE RHRHRYEFNN DYKAQYEAAG
MKCVGINPES DLVEIVEIPA LKWFIGTQFH PEYSSTVLNP HPLFVAFVKA AIENEKN
